ABSTRACT
Cardiometabolic disease arises from a complex interaction between many factors, including genetic, physiologic, behavioral, and environmental influences. The increases in rates of metabolic disorders over recent years suggest that genetics may play a relatively minor role, with increasing evidence for environmental (e.g., epigenetic) and behavioral effects, underpinning the present disease epidemic. In particular, alterations in the early-life nutritional environment (spanning the periconceptional period through to infancy) are now well established to result in a “programmed” predisposition to a range of metabolic and cardiovascular disorders in later life. In this context (preferentially termed the “developmental origins of health and disease or “DOHaD”), it has been shown in both human cohorts and experimental animal models that a range of altered early-life nutritional environments, including both under- and overnutrition, can lead to cardiometabolic disorders in offspring. Further, these effects can be amplified by the postnatal nutritional environment and also can be transmitted across generations, thus leading to cycle of disease. Although the mechanisms are not fully defined, this programming was initially considered an irreversible change in developmental trajectory. However, it has now been shown that, at least in pre-clinical models, programmed metabolic disorders are potentially reversible by nutritional or targeted therapeutic interventions during critical periods of development. Given that fixed genomic variation may only explain a small proportion of disease risk, there is an increasing interest in the role of epigenetics. As an example, epigenetic gene promoter methylation at birth has been associated with later adiposity in childhood. These findings suggest that a substantial component of disease risk may have a prenatal developmental basis and perinatal epigenetic analysis may therefore have utility in identifying individual vulnerability to later cardiometabolic disease.
